Critical technologies development to enable the use of synthetic siRNAs in crop protection.

• Grant number: 25/12703-3
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: February 01, 2026
• End date: January 31, 2028
• Field of knowledge: Agronomical Sciences - Agronomy - Plant Health
• Principal Investigator: Cristiane de Santis Alves
• Grantee: Cristiane de Santis Alves
• Principal investigators: Letícia Tsieme Gushi
• Associated researchers: Laudicéia Alves de Oliveira ; Marcelo Viana de Moraes
• Associated research grant: 23/14514-8 - Critical technologies development to enable the use of synthetic siRNAs in crop protection., AP.PIPE
• Associated scholarship(s): 26/00022-4 - Critical technologies development to enable the use of synthetic siRNAs in crop protection., BP.PIPE

Abstract

The utilization of interfering RNAs presents a viable alternative to managing the numerous instances of resistance to chemical control agents and sustainable pest management, diseases, and weeds. The primary justifications for this approach include its easy biodegradation, diverse potential sites of action, and most notably, the possibility of obtaining selective RNAs that specifically target a single species or biotype. This specificity enables selective control in situations where chemical agents, which interact with proteins, would not be effective.Although there are hundreds of patents on synthetic RNAs with potential applications in plant protection, they have not yet reached the market. The primary reasons for this include the stability of siRNAs under practical conditions of use and the challenges in developing delivery systems for these compounds that can overcome the barriers to entry of xenobiotics present in the target species.There are several approaches to enhancing the stability and optimizing the dynamics of synthetic RNAs for their use in agriculture, including the utilization of synthetic RNAs with double tapes, hairpins, specific surfactants, liposomes, vesicles, capsules, microparticles, and nanoparticles. Even when plants are not the intended target of RNAs, such as in pest, disease, and nematode control, they have been the preferred target for applications, serving as reservoirs and release systems for these organisms. In the case of ANNs with herbicide action, plants will always be the target of both control and applications.BioAtiva currently lacks the necessary financial capacity to develop and commercialize technologies based on RNAs. However, they have been acquiring the necessary conditions to develop these technologies. Additionally, they have established two types of partnerships with companies that develop these technologies:1. Evaluation of technologies developed by partner companies.2. Joint development of technologies with reimbursement for services and receipt of royalties in the event of success. These models are analogous to the ones employed by the company in the majority of studies involving xenobiotics. PiPe 1 was pivotal for BioAtiva's training and expansion of its workforce, as well as its development of molecular biology methods and LCMSMS necessary for studying the efficacy and dynamics of siRNAs. It introduced the company's work routines with Nicotiana benthamiana, which were fundamental to studying the dynamics and action of xenobiotics. Consequently, BioAtiva was qualified to study practically all related aspects of the route of tetrapyrrol/porphyrin synthesis in plants. By integrating molecular biology techniques and high-resolution or unit-resolution LCMSMS, BioAtiva will be able to monitor the dynamics, metabolism, and action of Protox inhibitor herbicides on weeds, cultivated plants, and the environment. Protox has emerged as a priority in the development of novel herbicides and transgenics resistant to them. Consequently, BioAtiva will be able to provide a comprehensive range of services in monitoring the resistance of weeds or cultivated plants to Protox inhibitors, including gene sequencing and the determination of expression levels; accumulation of route intermediate compounds and markers; evaluation of the dynamics and metabolism of the herbicides; evaluation of the functionality of antioxidant systems; characterization and occurrence of symptoms; photosynthetic performance and control levels. The primary goal of the proposed PiPe 2 is to finalize development and integrate all the aforementioned technologies. (AU)